Changes in the hepatitis B virus precore and core regions in association with the disappearance of hepatitis B e antigen in patients with chronic hepatitis B.

Disappearance of the hepatitis B e antigen (HBeAg) typically signals the remission of chronic hepatitis B; however, HBeAg defective variants have been identified in patients with HBeAg negative chronic hepatitis (CH). We studied the changes in the hepatitis B virus (HBV) genome associated with HBeAg clearance in four asymptomatic carriers (ASC) and in four patients with CH. Three ASC had a precore stop codon variant with the core region being wild-type or deleted. The other ASC had wild-type precore and core region. In all ASC, HBV levels were reduced markedly with two ASC converting HBV negative status via polymerase chain reaction. In contrast, patients with CH had continued high titers of HBV. In two patients, the precore region remained wild-type, but the core region contained a cleavage site mutation or was deleted. The precore variant was present in both ASC and CH, perhaps suggesting that it does not significantly influence hepatitis B activity.